The interaction of helminth infections with type 2 diabetes (T2D) has been a major area of research in the past few years. This paper, therefore, focuses on the systematic review of the effects of helminthic infections on metabolism and immune regulation related to T2D, with mechanisms through which both direct and indirect effects are mediated. Specifically, the possible therapeutic role of helminths in T2D management, probably mediated through the modulation of host metabolic pathways and immune responses, is of special interest. This paper discusses the current possibilities for translating helminth therapy from basic laboratory research to clinical application, as well as existing and future challenges. Although preliminary studies suggest the potential for helminth therapy for T2D patients, their safety and efficacy still need to be confirmed by larger-scale clinical studies.

Background: TERT promoter mutation (TPM) is an established biomarker in meningiomas associated with aberrant TERT expression and reduced progression-free survival (PFS). TERT expression, however, has also been observed even in tumours with wildtype TERT promoters (TP-WT). This study aimed to examine TERT expression and clinical outcomes in meningiomas. Methods: TERT expression, TPM status, and TERT promoter methylation of a multi-institutional cohort of meningiomas (n=1241) was assessed through nulk RNA sequencing (n=604), Sanger sequencing of the promoter (n=1095), and methylation profiling (n=1218). 380 Toronto meningiomas were used for discovery, and 861 external institution samples were compiled as a validation cohort. Results: Both TPMs and TERTpromoter methylation were associated with increased TERT expression and may represent independent mechanisms of TERT reactivation. TERT expression was detected in 30.4% of meningiomas that lacked TPMs, was associated with higher WHO grades, and corresponded to shorter PFS, independent of grade and even among TP-WT tumours. TERT expression was associated with a shorter PFS equivalent to those of TERT-negative meningiomas of one higher grade. Conclusions: Our findings highlight the prognostic significance of TERT expression in meningiomas, even in the absence of TPMs. Its presence may identify patients who may progress earlier and should be considered in risk stratification models.

Background: The WHO grade of meningioma was updated in 2021 to include homozygous deletions of CDKN2A/B and TERT promotor mutations. Previous work including the recent cIMPACT-NOW statement have discussed the potential value of including chromosomal copy number alterations to help refine the current grading system. Methods: Chromosomal copy number profiles were inferred from from 1964 meningiomas using DNA methylation. Regularized Cox regresssion was used to identify CNAs independenly associated with post-surgical and post-RT PFS. Outcomes were stratified by WHO grade and novel CNAs to assess their potential value in WHO critiera. Results: Patients with WHO grade 1 tumours and chromosome 1p loss had similar outcomes to those with WHO grade 2 tumours (median PFS 5.83 [95% CI 4.36-Inf] vs 4.48 [4.09-5.18] years). Those with chromosome 1p loss and 1q gain had similar outcomes to those with WHO grade 3 cases regardless of initial grade (median PFS 2.23 [1.28-Inf] years WHO grade 1, 1.90 [1.23-2.25] years WHO grade 2, compared to 2.27 [1.68-3.05] years in WHO grade 3 cases overall). Conclusions: We advocate for chromosome 1p loss being added as a criterion for a CNS WHO grade of 2 meningioma and addition of 1q gain as a criterion for a CNS WHO grade of 3.

Background: We previously developed a DNA methylation-based risk predictor for meningioma, which has been used locally in a prospective fashion. As a follow-up, we validate this model using a large prospective cohort and introduce a streamlined next-generation model compatible with newer methylation arrays. Methods: The performance of our next-generation predictor was compared with our original model and standard-of-care 2021 WHO grade using time-dependent receiver operating characteristic curves. A nomogram was generated by incorporating our methylation predictor with WHO grade and extent of resection. Results: A total of 1347 meningioma cases were utilized in the study, including 469 prospective cases from 3 institutions and a retrospective cohort of 100 WHO grade 2 cases for model validation. Both the original and next-generation models significantly outperformed 2021 WHO grade in predicting postoperative recurrence. Dichotomizing into grade-specific risk subgroups was predictive of outcome within both WHO grades 1 and 2 tumours (log-rank p<0.05). Multivariable Cox regression demonstrated benefit of adjuvant radiotherapy in high-risk cases specifically, reinforcing its informative role in clinical decision making. Conclusions: This next-generation DNA methylation-based meningioma outcome predictor significantly outperforms 2021 WHO grading in predicting time to recurrence. This will help improve prognostication and inform patient selection for RT.

Background: Meningiomas exhibit considerable heterogeneity. We previously identified four distinct molecular groups (immunogenic, NF2-wildtype, hypermetabolic, proliferative) which address much of this heterogeneity. Despite their utility, the stochasticity of clustering methods and the requirement of multi-omics data limits the potential for classifying cases in the clinical setting. Methods: Using an international cohort of 1698 meningiomas, we constructed and validated a machine learning-based molecular classifier using DNA methylation alone. Original and newly-predicted molecular groups were compared using DNA methylation, RNA sequencing, whole exome sequencing, and clinical outcomes. Results: Group-specific outcomes in the validation cohort were nearly identical to those originally described, with median PFS of 7.4 (4.9-Inf) years in hypermetabolic tumors and 2.5 (2.3-5.3) years in proliferative tumors (not reached in the other groups). Predicted NF2-wildtype cases had no NF2 mutations, and 51.4% had others mutations previously described in this group. RNA pathway analysis revealed upregulation of immune-related pathways in the immunogenic group, metabolic pathways in the hypermetabolic group and cell-cycle programs in the proliferative group. Bulk deconvolution similarly revealed enrichment of macrophages in immunogenic tumours and neoplastic cells in hypermetabolic/proliferative tumours. Conclusions: Our DNA methylation-based classifier faithfully recapitulates the biology and outcomes of the original molecular groups allowing for their widespread clinical implementation.

The frequency responses of circulation control and separation control using mini-spoilers for loads attenuation on plunging swept and unswept wings were compared in a water tunnel study. At the pre-stall angle-of-attack, the effectiveness of the spoilers significantly diminishes with increasing reduced frequency of the plunging motion. For the leading-edge spoiler, this happens because the roll-up of the vorticity promotes flow reattachment and reduces the effectiveness of loads attenuation. For the trailing-edge spoiler, the effectiveness of lift attenuation also decreases with increasing reduced frequency, due to the shedding of leading-edge vortices and immersion of the trailing-edge spoiler in the separated flow. The decay of the frequency response for both types of spoilers is similar, implying that it is dictated by the flow separation near the leading edge of the wing in both cases. With increasing sweep angle of the wings, the spoilers’ effectiveness decreases significantly in comparison to the unswept wing. Strong spanwise flow develops for the leading-edge spoiler, which sheds a streamwise vortex, with the same direction of rotation as the wing-tip trailing vortex. This causes partial reattachment of the flow and reduction of the separation area behind the spoiler. With increasing reduced frequency, strong leading-edge vortices dominate the flow over the wing. The leading-edge vortices generate additional vortex lift and also cause the trailing-edge spoiler to be immersed in the massively separated flows. Both factors reduce the effectiveness of the spoilers.

This study examined the variability of language profiles in Spanish–English bilingual children with and without developmental language disorder (DLD). The data included 529 children between the ages of 5 and 10 years. Eighty-eight of these children were identified as having DLD. A latent profile analysis was conducted based on children’s morphosyntax and semantics performance in Spanish and English. The optimal model identified five different profiles, illustrating the heterogeneity in bilingual development. Children with DLD were observed across all profiles, but most were classified in the only two profiles where lower morphosyntax than semantic performance was observed across languages. These results show the variability in both bilingual children with and without DLD. Additionally, the hallmark deficit of DLD in morphosyntax was confirmed, with the morphological weakness being observed in each of the bilingual children’s languages. Children’s background factors (age, maternal education and language exposure) were associated with profile characteristics.

Through a series of example research studies, we illustrate processes in translating case report forms to increase language diversity in study populations while simultaneously highlighting implications for data collection and analyses. The Northwestern University Data Analysis and Coordinating Center manages the translation of participant-facing study documents into languages other than English through a process that has been refined over several years, adjusting for changes in technical capabilities in electronic case report forms. This approach to manage, examine for context, and implement certified case report form translations offers an efficient workflow to streamline data capture in multiple languages.

The stars of the Milky Way carry the chemical history of our Galaxy in their atmospheres as they journey through its vast expanse. Like barcodes, we can extract the chemical fingerprints of stars from high-resolution spectroscopy. The fourth data release (DR4) of the Galactic Archaeology with HERMES (GALAH) Survey, based on a decade of observations, provides the chemical abundances of up to 32 elements for 917 588 stars that also have exquisite astrometric data from the Gaia satellite. For the first time, these elements include life-essential nitrogen to complement carbon, and oxygen as well as more measurements of rare-earth elements critical to modern-life electronics, offering unparalleled insights into the chemical composition of the Milky Way. For this release, we use neural networks to simultaneously fit stellar parameters and abundances across the whole wavelength range, leveraging synthetic grids computed with Spectroscopy Made Easy. These grids account for atomic line formation in non-local thermodynamic equilibrium for 14 elements. In a two-iteration process, we first fit stellar labels to all 1 085 520 spectra, then co-add repeated observations and refine these labels using astrometric data from Gaia and 2MASS photometry, improving the accuracy and precision of stellar parameters and abundances. Our validation thoroughly assesses the reliability of spectroscopic measurements and highlights key caveats. GALAH DR4 represents yet another milestone in Galactic archaeology, combining detailed chemical compositions from multiple nucleosynthetic channels with kinematic information and age estimates. The resulting dataset, covering nearly a million stars, opens new avenues for understanding not only the chemical and dynamical history of the Milky Way but also the broader questions of the origin of elements and the evolution of planets, stars, and galaxies.

Discretionary foods that are energy-dense and nutrient-poor contribute to over one third of total energy intake in Australian children and adults, and the typical portion sizes of many discretionary foods have increased significantly in the last two decades(1). The portion size norms (described as a typical perception of how much of a given food people choose to eat at a single eating occasion) are likely to have increased concurrently, with larger sizes now being considered the new normal(2). Public health interventions are urgently needed to reduce the portion size norms and consumption of discretionary foods(3), but the acceptability of such interventions remains unknown. Therefore, this qualitative study aimed to gain insights into consumers’ attitudes towards potential interventions targeted at promoting portion control of discretionary foods. Four online focus group sessions were conducted via Zoom with healthy Australian adults who regularly consume discretionary foods. A question guide was developed to gather participants’ perspectives around four potential public health interventions; reduction of the default serving sizes, increasing serving size options, changes to package sizes, and improving serving size labelling. A female facilitator moderated all focus groups, with a second moderator present to capture other relevant details. Collected data were analysed using a hybrid approach combining deductive and inductive thematic analyses. A total of 35 participants completed the study (19 females, mean age 38 ± 14 years). Participants identified the current food environment as promoting overconsumption; larger serving sizes were reported to be more ubiquitous and better value for money than smaller size options. An overall positive attitude towards the proposed interventions was noted. Out of the four proposed interventions, participants considered the most acceptable intervention to be providing a wider range of serving size options while maintaining a consistent unit price. Other acceptable interventions included reducing the default serving sizes with concurrent price reduction; education and clear guidance around portion size selection (for example, the involvement of health professionals to promote portion control, along with relevant recommendations of appropriate portion sizes from health authorities); more practical on-pack serving size suggestions; and innovative package designs that enable better portion control without contributing to food and plastic waste. In conclusion, participants identified a need for and were in support of interventions aimed at the portion control of discretionary foods. Further research should focus on examining the feasibility and effectiveness of the potential interventions to reduce the purchasing and consumption of large serving sizes. More efforts from public health authorities are required to develop practical and tailored recommendations for consumers around appropriate portion sizes for discretionary foods. Collaboration with the food industry and policy makers is also necessary for implementing public health interventions to reduce the excessive intake of discretionary foods.

Ecological momentary assessment (EMA) may be a valid and acceptable method of assessing dietary intake in young adults(1). EMA may overcome some of the limitations associated with traditional dietary assessment methods such as high respondent burden and memory biases(2) by capturing time-sensitive data via concise dietary surveys. However, most dietary EMA studies either deliver signal-contingent EMAs at fixed intervals or rely on the user’s memory to self-initiate event-contingent EMAs whenever they ate. This may be inappropriate for young adults due to their highly variable eating patterns(1). Young adults are particularly vulnerable to weight gain due to major life transitions and, for this population, dietary information may need to be collected near real-time to improve recall accuracy(3). Therefore, the aim of this study was to examine the feasibility (response rate) and acceptability of an EMA protocol that delivered dietary surveys at times personalised to young adults’ (18–30 years) eating patterns and to compare this to the feasibility and acceptability of EMAs delivered at fixed intervals. A randomised, double-blinded crossover design with two four-day treatment arms was used. In one arm, participants received six EMAs per day at fixed intervals. In the other arm, EMAs were delivered at times tailored to participants’ usual eating schedules (ranged between two to six EMAs per day). Usual eating schedules were determined using time-stamped food and beverage images captured by participants over the four days immediately prior to treatments. EMA questions included, but were not limited to, time of consumption and type of food or beverage group consumed. Response rates were calculated as the percentage of EMAs responded to out of the EMAs delivered. At the end of each arm, participants completed an acceptability survey assessing their opinion of the number of EMAs per day, length of the EMAs, and number of recording days. Twenty-three subjects were included (13 female; mean age 26, SD 2.1 years). Mean response rates of the fixed interval and personalised schedule treatments were 65.1% (SE 3.7%) and 66.3% (SE 3.7%), respectively. Compared to the fixed interval treatment, EMAs delivered during the personalised schedule treatment did not align closer with participants’ eating times; the average time difference between EMA delivery and reported eating time was 1.7 hours for both treatments. Participants from both treatments reported receiving too many EMAs per day but found the length of the EMA and number of days of recording to be ‘just right’. In conclusion, EMAs delivered on a personalised schedule may not improve participant adherence. Due to the irregular nature of young adults’ eating patterns, timing of EMA delivery is difficult to tailor. Future definitive trials should use more sophisticated methods of personalisation such as wearable sensors to trigger event-contingent EMAs.

Ice shelves affect the stability of ice sheets by supporting the mass balance of ice upstream of the grounding line. Marine ice, formed from supercooled water freezing at the base of ice shelves, contributes to mass gain and affects ice dynamics. Direct measurements of marine ice thickness are rare due to the challenges of borehole drilling. Here we assume hydrostatic equilibrium to estimate marine ice distribution beneath the Amery Ice Shelf (AIS) using meteoric ice-thickness data obtained from radio-echo sounding collected during the Chinese National Antarctic Research Expedition between 2015 and 2019. This is the first mapping of marine ice beneath the AIS in nearly 20 years. Our new estimates of marine ice along two longitudinal bands beneath the northwest AIS are spatially consistent with earlier work but thicker. We also find a marine ice layer exceeding 30 m of thickness in the central ice shelf and patchy refreezing downstream of the grounding line. Thickness differences from prior results may indicate time-variation in basal melting and freezing patterns driven by polynya activity and coastal water intrusions masses under the ice shelf, highlighting that those changes in ice–ocean interaction are impacting ice-shelf stability.

The formation of Kelvin–Helmholtz-like rollers (referred to as K–H rollers) over riblet surfaces has been linked to the drag-increasing behaviour seen in certain riblet geometries, such as sawtooth and blade riblets, when the riblet size reaches sufficiently large viscous scales (Endrikat et al. (2021a), J. Fluid Mech. 913, A37). In this study, we focus on the sawtooth geometry of fixed physical size, and experimentally examine the response of these K–H rollers to further increases in viscous scaled riblet sizes, by adopting the conventional approach of increasing freestream speeds (and consequently, the friction Reynolds number). Rather than continual strengthening, the present study shows a gradual weakening of these K–H rollers with increasing sawtooth riblet size. This is achieved by an analysis of the roller geometric characteristics using both direct numerical simulations and hot-wire anemometry databases at matched viscous scaled riblet spacings, with the former used to develop a novel methodology for detecting these rollers via streamwise velocity signatures (e.g. as acquired by hot wires). Spectral analysis of the streamwise velocity time series, acquired within riblet grooves, reveals that the frequencies (and the streamwise wavelengths) of the K–H rollers increase with increasing riblet size. Cross-correlation spectra, estimated from unique two-point hot-wire measurements in the cross-plane, show a weakening of the K–H rollers and a reduction in their wall-normal coherence with increasing riblet size. Besides contributing to our understanding of the riblet drag-increasing mechanisms, the present findings also have implications for the heat transfer enhancing capabilities of sawtooth riblets, which have been associated previously with the formation of K–H rollers. The present study also suggests conducting future investigations by decoupling the effects of viscous scaled riblet spacing and friction Reynolds numbers, to characterise their influence on the K–H rollers independently.